The thrust of this research investigation is 1) to determine what intracellular mechanisms control the events of secretion granule fusion to the plasma membrane and granule lysis in insulin release, in particular to characterize the possible relationship of calmodulin and cyclic AMP-induced protein phosphorylation in evoking intracellular events promoting granule fusion and/or granule lysis, 2) to determine wherein various secretagogues may effect various intracellular mechanisms in inducing insulin release, 3) to validate the hypothesis that the recruitment of somatostatin receptors may be used as a determinant for measuring secretion vesicle fusion to the plasma membrane, and hormone release as a separate marker for granule lysis and 4) to determine whether the recruitment of somatostatin receptors is significant in modulating somatostatin inhibition of insulin release induced by various secretagogues. The methodology basically consists of determining somatostatin binding, insulin release and phosphorylation of certain specific proteins (which are thought to reflect calmodulin and also cyclic AMP dependent protein kinase activity). These determinants will be measured in the presence of various factors known to either stimulate or suppress insulin release. The long term objectives of this research are to characterize more precisely some of the important events in exocytosis which play a role in insulin release. The long term significance of this research is hopefully a better understanding of the precise defects in insulin release which may exist in various patients with diabetes mellitus.